Meningitis outbreak sparks investigations, lawsuits, fears

In this Oct. 16, 2012, file photo, a Food and Drug Administration Agent stands at the doorway of New England Compounding Center in Framingham, Mass. Michigan’s attorney general announced Tuesday, March 26, 2013, he is seeking a criminal investigation into the deaths of 17 residents from contaminated steroids supplied by a Massachusetts pharmaceutical company. He said Michigan leads the country in patients affected by the fungal meningitis outbreak. (AP Photo/Bill Sikes, File)

DETROIT — In September, Milda Mattila became unsteady on her legs. Soon, she was unable to walk.

The 87-year-old South Lyon, Mich., woman had been infected with fungal meningitis through a tainted steroid shot meant to relieve back pain.

“Why did I have to get this?” she asked her family.

That question fills households and hospital rooms as hundreds of people struggle with the physical, emotional and financial scars left in the wake of the national fungal meningitis outbreak that has killed at least 51 people, including 17 Michigan residents. Nationwide, 730 people have fallen ill, including 259 in Michigan.

Advertisement

Investigations of the compounding pharmacy that produced the tainted shots are ongoing. Lawmakers and officials at federal and state agencies are trying to make sure that a similar crisis never happens again. Patients face an uncertain future with no ready answers on whether they will ever fully recover or who will pay their mounting hospital bills. Lawsuits are pending, but the company behind the outbreak has filed for bankruptcy.

“It all needs to change: how these drugs are produced, all the regulations, what the public is informed of. Everything needs to change. All these people died innocently,” said 45-year-old Lydia Doyon of Oxford, who became sick after getting a fungus-tainted steroid shot.

The crisis that erupted last September sparked outrage nationwide and prompted calls for greater oversight of compounding pharmacies. At such pharmacies, pharmacists mix and modify drugs to suit the needs of an individual patient who has a doctor’s prescription.

The Food and Drug Administration licenses drug manufacturers but not compounding pharmacies, leaving it primarily up to states to monitor them. Compounded drugs are not approved by the FDA, but the agency does have some authority over them when it receives a report of contamination or other problems.

Officials said the Framingham, Mass.-based New England Compounding Center (NECC) was operating - in violation of state laws and regulations - more like a big drug manufacturer by distributing large amounts of its products for general use at facilities instead of requiring individual prescriptions.

“What some of these pharmacies are doing is they crossed the line, and they’re manufacturing, and that’s what (the) NECC was doing. I don’t mean a little bit. I mean a lot,” said Michael Wissel, pharmacy services manager for the Michigan Department of Licensing and Regulatory Affairs. “They’re actually creating a product for a huge number of people. ... There’s a whole level of regulatory management that’s just not there.”

Beginning in May 2012, the NECC shipped 17,000 vials of contaminated preservative-free methylprednisolone acetate from three lots to facilities in 23 states, leading to the deadly outbreak.

In 2004, the NECC was licensed to fill prescriptions for Michigan residents. In the years that followed, the state never received any complaints about the pharmacy, Wissel said.

But according to a memo released last fall before congressional hearings, the pharmacy board in Massachusetts had investigated at least 12 complaints involving the NECC or Barry Cadden, the president and co-owner of the company, prior to the outbreak. The report also said the FDA had conducted three series of inspections based on separate sets of allegations.

“Some of the violations observed by regulators as early as 2002 include the company’s failure to maintain adequate safeguards for sterile injectable products - the very issue at the center of the current meningitis outbreak,” the memo said.

The NECC’s past problems took center stage at a Nov. 14 hearing before members of the House Energy and Commerce Committee.

“After a tragedy like this, the first question we all ask: Could this have been prevented?” then-U.S. Rep. Cliff Stearns, R-Fla., asked. “After an examination of documents produced by the Massachusetts Board of Pharmacy and the U.S. Food and Drug Administration, the answer appears to be ‘yes.’ “

At the hearing, Cadden repeatedly invoked his Fifth Amendment right not to testify.

When investigators from the Massachusetts Department of Public Health visited the NECC on Sept. 26, after the company voluntarily recalled the tainted steroids, they reported finding workers trying to clean sterile compounding areas. There were signs that bleach had been used.

Inspections showed “serious health and safety deficiencies,” according to a report from the health department. Among them: puddles of water around a leaky boiler; heavily soiled mats that trap contaminants from shoes prior to entering a clean room where sterile drugs are produced, and residue left on powder hoods, which are used to protect pharmacists from inhaling substances while they’re working.

According to a FDA report, inspectors on Oct. 2 found that 83 of 321 vials of methylprednisolone acetate in a bin contained what appeared to be a “greenish-black foreign matter.” Seventeen vials had “white filamentous material.” The FDA said it tested 50 vials from the same lot and found the presence of microbial growth in all of them.

Inspectors found residue on autoclave devices used for sterilization and said the center failed to test the devices or follow proper sterilization procedures. The NECC’s own records showed that mold and bacteria had been found in clean rooms in the preceding months, the report said.

“In my general sense, I think it’s as simple as an unregulated industry that was allowed to expand so fast without government oversight that shortcuts were taken to try to get more product manufactured to make more money,” said Terry Dawes, a Southfield attorney who represents people injured by the injections.

The growth of the compounding industry in recent years has been fueled, in part, by medication shortages, said Larry Wagenknecht, CEO of the Michigan Pharmacists Association. The industry makes up 1 percent to 3 percent of the $300 billion U.S. prescription market, according to information from the International Academy of Compounding Pharmacists.

At the congressional hearing, FDA Commissioner Margaret Hamburg said giving the agency stronger, clearer authority would enable more effective regulation of the compounding industry.

“As it is, our authority over compounding is limited, unclear and contested, and in the face of differing views in Congress and the courts about (the) FDA’s authority and continuing challenges by industry, the agency has struggled with how to chart an effective course to protect the public health.”

Days after issuing its recall of the steroids, the NECC recalled all of its products and ceased operations. Just before Christmas, it filed for bankruptcy.

It is facing hundreds of lawsuits and ongoing investigations by the FDA, the federal Centers for Disease Control and Prevention and the Massachusetts Board of Pharmacy.

In Michigan, Attorney General Bill Schuette announced last month that he wants to convene a grand jury to investigate for possible criminal charges.

Dawes represents 80 patients from Michigan who received the tainted shots. The attorney was one of nine people selected for a committee of unsecured creditors that will represent the interests of all creditors, including the outbreak victims, as the bankruptcy case proceeds through a Massachusetts court.

An adversary complaint filed in the case alleges that in the year leading up to the bankruptcy filing, the NECC’s owners transferred or paid themselves or their related companies $21 million.

“These transfers continued well beyond the appearance of contaminated vials and their exposure to hundreds of people ... and continued even beyond the reports of illnesses and deaths that allegedly resulted from the fungal contamination,” leaving the company with insufficient assets to satisfy the claims against it, the complaint says.

Marc Lipton, another Michigan attorney representing victims, said a bankruptcy judge placed liens on the homes of the NECC’s owners and froze certain financial accounts.

It’s hard to say when victims will be compensated or how much they will receive. Dawes hopes a compensation fund and a system for people to submit claim forms will be established by the end of this year.

Mark Klaserner, 57, of Milford is one of dozens of people from Michigan who have filed lawsuits against the NECC. Although he has health insurance, Klaserner is worried about potentially huge medical bills after spending about six weeks in St. Joseph Mercy Ann Arbor.

“It’s going to bankrupt me,” Klaserner said. “What I’ll end up doing is spending what I have left in an annuity, what I was saving for retirement, and use my pension. It’s horrible.”

According to Laura Blodgett, a spokeswoman for St. Joseph Mercy, the outpatient cost of voriconazole, one of two main antifungal drugs used in treatment, ranges from $3,000 to $8,000 a month, depending on the dosage. She said the hospital has helped patients tap into drug companies’ financial assistance programs.

In November, members of the Senate Health, Education, Labor and Pensions Committee sent letters to the boards of pharmacy in each state, asking about their oversight of compounding pharmacies and how they responded to the outbreak.

Wissel, the pharmacy services manager for Michigan’s licensing and regulations department, said a state inspector visited one of the four Michigan clinics involved in the outbreak in October and found several vials, including multi-dose vials, of the steroid labeled with the clinic’s name but not individual patient prescription labels, as required. The state suspended the NECC’s Michigan pharmacy license, although by then, the company had ceased operations.

Michigan has about 3,000 licensed pharmacies, including those that are based out of state. All are legally allowed to compound drugs. Most do not perform sterile compounding, which involves processes to ensure products such as injectable drugs are free of contaminants.

Wagenknecht said the Michigan Public Health Code says that all pharmacists are responsible for the strength, quality and purity of drugs dispensed with a prescription. But because there are no state licenses or mandates that apply specifically to compounding pharmacies or sterile compounding, the practice is difficult to track.

Following the outbreak, the state began to try to pin down the number of compounding pharmacies in Michigan. Wissel said the state has 70-80 pharmacies that engage in sterile compounding. About 50 have been inspected so far. More inspections are planned.

Wissel also said there are between 10 and 30 facilities in the state that only do compounding.

Staff at the Michigan Department of Licensing and Regulatory Affairs is working with the Michigan Board of Pharmacy to draft legislation to tighten regulations so the state can keep better tabs on compounding pharmacies. Wissel said it would provide for regular inspections of such pharmacies and require background checks of pharmacy owners in addition to the background checks already performed on pharmacists.

The state also intends to ask about compounding practices when pharmacy licenses are renewed.

FDA officials said the agency is committed to working with Congress, the states and the medical community to put an appropriate regulatory system in place.

In a March 22 blog post, Hamburg called for legislation that would establish minimum federal standards for pharmacies that compound and widely distribute sterile drugs.

“(The) FDA must have clear authority to proactively inspect pharmacies to determine the scope and nature of their operations,” the FDA chief said.

Hamburg wrote that in the last two months, the FDA has inspected more than 30 state-licensed pharmacies that produce sterile drug products. Noting two recent recalls, she said there continues to be serious problems at some pharmacies.

A March 27 posting on the website of National Association of Boards of Pharmacy said a compounding pharmacy in New Jersey voluntarily recalled all of its compounded products after a Connecticut hospital discovered mold particles in five bags of an intravenous solution.

As the outbreak unfolds, Mattila fights for her life. She developed both fungal meningitis and an epidural abscess.

In the first week of December, two months after she was first hospitalized, she became gravely ill with a C. difficile infection. She was put on a respirator. Doctors recommended gathering family members for final goodbyes.

Mattila surprised everyone when she began to improve. But there have been other battles, including pneumonia and a bedsore. She has had a tracheostomy and a feeding tube inserted in her abdomen.

Mattila’s family members celebrated her birthday in November at her bedside. They brought her balloons Dec. 16 to celebrate her 68-year wedding anniversary to her husband, Ralph. On Christmas, they gave her presents and sang carols.

One of her six children, daughter Carol McKee, brought her palms on Palm Sunday.

Before meningitis, Mattila’s only health ailment was the back pain that prompted the steroid injection.

“It’s very difficult to see someone so active to have to go through this. It’s very heartbreaking,” McKee said. “It consumes every moment of our lives.